PURPOSE: Treatment with antiplatelet drugs is a key element of secondary stroke prevention. We investigated long-term antiplatelet drug use in stroke patients with a focus on non-persistence. METHODS: Population-based prescription register data were used to determine antiplatelet drug use in a cohort of stroke patients discharged from a Danish neurology department. The antiplatelet drugs comprised acetylsalicylic acid (ASA), clopidogrel and dipyridamole (if combined with ASA use). Non-persistence was defined as failure to present a prescription for antiplatelet drugs within 180 days after the dosage of a previous prescription had run out, or within 180 days after discharge. Cox regression was used to identify risk factors for non-persistence. RESULTS: The cohort comprised 503 patients with ischaemic stroke discharged in 1999-2001. During follow-up (median 2.8 years, interquartile range 0.8-7.8 years), 486 of the subjects presented prescriptions for antiplatelets. Most subjects used a dual regimen of ASA and dipyridamole (N = 320). Of 110 non-persistent subjects in this group, 64 stopped using ASA, but continued to use dipyridamole in monotherapy. Overall, 181 patients (36 %) were non-persistent. Stroke severity was inversely associated with the risk of non-persistence [NIHSS score on admission 0-3 (reference); 4-6: hazard risk (HR) 0.87, 95 % confidence interval (CI) 0.61-1.25; 7+: HR 0.47, 95 % CI 0.29-0.74]. CONCLUSIONS: Long-term non-persistence with antiplatelet treatment was high and more pronounced in our patients with less severe stroke. Our findings on the use of ASA and dipyridamole indicate that non-persistence may in part be amenable to simple intervention measures.